Seizures after initiation of rewarming in cooled infants with hypoxic ischaemic encephalopathy.

BACKGROUND: Seizures after initiation of rewarming from therapeutic hypothermia for neonatal encephalopathy are well recognised but not easy to predict. METHODS: A secondary analysis was performed of NEOLEV2 trial data, a multicentre randomised trial of levetiracetam versus phenobarbital for neonatal seizures. Enrolled infants underwent continuous video EEG (cEEG) monitoring. The trial data were reviewed for 42 infants with seizures during therapeutic hypothermia and 118 infants who received therapeutic hypothermia but had no seizures on cEEG. RESULTS: Overall, 112 of 160 (70%) had cEEG monitoring continued until rewarming was completed. Of the 42 infants with prior seizures, there were 30 infants with valid cEEG available and seizures occurred following the initiation of rewarming in 8 (26.6%). For the 118 seizure-naive infants, 82 (69.5%) continued cEEG until either rewarming was completed or 90 h of age and none had documented seizures. CONCLUSION: Overall, just over a quarter of infants with prior seizures had cEEG evidence of at least one seizure in the 24 h after initiation of rewarming but no seizure-naive infant had cEEG evidence of seizure(s) on rewarming. Critically, by reporting the two groups separately, the data can provide guidance on the duration of EEG monitoring. IMPACT: Infants with hypoxic ischaemic encephalopathy who have cEEG evidence of seizures during therapeutic hypothermia have a significant risk of further seizures on rewarming. For infants with hypoxic ischaemic encephalopathy but no cEEG evidence of seizures during therapeutic hypothermia, there is very little risk of de novo seizures. Ongoing work utilising large cohorts may generate EEG criteria that refine estimates of risk for rewarming seizures. Based on current experience, if seizures have occurred during therapeutic hypothermia for hypoxic ischaemic encephalopathy, the EEG monitoring should be continued during rewarming and for 12 h thereafter to minimise the risk of missing an event.

Diagnostic yield of pediatric and prenatal exome sequencing in a diverse population.

The diagnostic yield of exome sequencing (ES) has primarily been evaluated in individuals of European ancestry, with less focus on underrepresented minority (URM) and underserved (US) patients. We evaluated the diagnostic yield of ES in a cohort of predominantly US and URM pediatric and prenatal patients suspected to have a genetic disorder. Eligible pediatric patients had multiple congenital anomalies and/or neurocognitive disabilities and prenatal patients had one or more structural anomalies, disorders of fetal growth, or fetal effusions. URM and US patients were prioritized for enrollment and underwent ES at a single academic center. We identified definitive positive or probable positive results in 201/845 (23.8%) patients, with a significantly higher diagnostic rate in pediatric (26.7%) compared to prenatal patients (19.0%) (P = 0.01). For both pediatric and prenatal patients, the diagnostic yield and frequency of inconclusive findings did not differ significantly between URM and non-URM patients or between patients with US status and those without US status. Our results demonstrate a similar diagnostic yield of ES between prenatal and pediatric URM/US patients and non-URM/US patients for positive and inconclusive results. These data support the use of ES to identify clinically relevant variants in patients from diverse populations.

Early Identification of Cerebral Palsy Using Neonatal MRI and General Movements Assessment in a Cohort of High-Risk Term Neonates.

BACKGROUND: Cerebral palsy (CP) is the most common motor disability of childhood. Its early identification is an important priority for parents and is critical for access to early intervention resources, which may optimize function. METHODS: A prospective cohort of term neonates at high risk for CP was assessed by neonatal magnetic resonance imaging (MRI) to determine myelination of the posterior limb of the internal capsule, General Movements Assessment to assess typical fidgety movements at age three months, and followed to at least age two years to determine diagnosis of CP based on neurological examination. RESULTS: Seven of 58 children developed CP (12%), two with moderate/severe CP. Sensitivity and specificity for abnormal myelination of the posterior limb of the internal capsule were (PLIC) was 29% and 94%, and for absent fidgety movements, 29% and 98%, respectively. Negative predictive value of both absent myelination of the PLIC and absent fidgety movements was 90% (79% to 96%) for any CP and 98% (90% to 100%) for moderate/severe CP cerebral palsy. None of the children with both normal PLIC and normal fidgety movements had moderate/severe CP. CONCLUSION: Normal neonatal MRI and General Movements Assessment at age three months are reassuring that a high-risk term-born child is at low risk for moderate/severe CP. These results are important for counseling parents and individualizing therapy resources in the community.

Cerebral oxygen balance is impaired during repair of aortic coarctation in infants and children.

OBJECTIVE: During repair of aortic coarctation through a left thoracotomy without cardiopulmonary bypass, clamping the proximal transverse aortic arch occludes antegrade flow to the left carotid and vertebral arteries. It is assumed that flow through the right carotid and vertebral arteries is adequate for cerebral perfusion. The study objective is to determine whether aortic occlusion impairs left hemispheric cerebral oxygen balance measured by near-infrared spectroscopy. METHODS: In 18 children having repair of aortic coarctation, we measured the maximum change and integral for hemoglobin D (difference of oxyhemoglobin and deoxyhemoglobin), total oxygenation index, and the redox state of cytochrome aa3. Thirteen subjects had recordings from the left hemisphere to test the hypothesis that aortic occlusion impairs left hemispheric oxygen balance. Five subjects had recordings from the right hemisphere for comparison. RESULTS: After aortic clamping, a significant decrease in hemoglobin D was observed in recordings from the left hemisphere compared with those from the right hemisphere (P = .03, maximum change in hemoglobin D). Total oxygenation index and cytochrome aa3 were generally preserved. There was an inverse linear relationship for the change in hemoglobin D during clamp application and after removal (Spearman rho = -0.74), with increased hemoglobin D after clamp removal in those subjects with the greatest decrease of hemoglobin D during arch occlusion. Linear regression analysis identified nitroprusside administration as significantly associated with a decrease in hemoglobin D (P < .001). CONCLUSIONS: Significant impairment in left hemispheric cerebral oxygen balance was identified during arch clamping. The neurodevelopmental significance of impaired cerebral oxygen balance detected by near-infrared spectroscopy during aortic coarctation repair remains to be elucidated.

Teaching neuroimages: infant with glutaric aciduria type 1 presenting with infantile spasms and hypsarrhythmia.

A 7-month-old boy with glutaric aciduria type 1 (GA1) presented with 1 week of clustered flexor spasms. Examination revealed mild axial hypotonia without encephalopathy. Video-EEG monitoring revealed hypsarrhythmia and infantile spasms (figure, A). MRI showed acute basal ganglia injury (figure, B). After 3 weeks of prednisolone treatment, 5-month follow-up showed continued resolution of hypsarrhythmia and spasms.

Intraparenchymal hemorrhage in a neonate with cleidocranial dysostosis.

We present a case of intraparenchymal hemorrhage in a neonate with cleidocranial dysostosis, a skeletal dysplasia that leads to delayed skull ossification. The patient's details are reported, including neuroimaging, photographs of classic dysmorphic features, and genetic testing. After spontaneous vaginal birth, the patient was hypotonic and encephalopathic, with unusually large and boggy fontanelles. No palpable bone overlay his bilateral temporal lobes, and his facial features were multiply dysmorphic. The patient's father exhibited similar facial features and congenital absence of the right clavicle, suggesting cleidocranial dysostosis. Magnetic resonance imaging at age 4 days confirmed a large right temporal lobe intraparenchymal hemorrhage, with extensive subarachnoid hemorrhage overlying both temporal and parietal lobes. A clinical diagnosis of cleidocranial dysostosis was confirmed by testing of the RUNX2 gene, which revealed a novel sequence alteration predicted to be disease-causing. Given that no palpable bone overlay the location of brain hemorrhage, and no other cause for hemorrhage was identified, we attribute the temporal lobe hemorrhage to forces on the skull incurred during normal vaginal delivery in the setting of decreased skull ossification.